Lignin hydrogel sensor with anti-dehydration, anti-freezing, and reproducible adhesion prepared based on the room-temperature induction of zinc chloride-lignin redox system.

In recent years, flexible sensors constructed mainly from hydrogels have received increasing attention. However, conventional hydrogels need to be prepared by high-temperature or radiation-induced polymerization reactions, which limits their practical applications due to their suboptimal electrical conductivity and weak mechanical properties. In this paper, using sodium lignosulfonate as the raw material, a dynamic catechol-quinone redox system formed by lignin­zinc ions was constructed to initiate rapid free radical polymerization of acrylamide (AM) monomer at room temperature. In addition, Deep eutectic solvent (DES) can form a strong hydrogen bonding network within the molecules and between the molecules of the hydrogel, resulting in a hydrogel with good tensile properties (hydrogel elongation at break of 727.19 %, breaking strength of 84.09 kPa), and provides the hydrogel with high electrical conductivity, anti-dehydration, anti-freezing, and anti-bacterial properties. Meanwhile, the addition of lignin also improved the adhesion and UV resistance of the hydrogel. This hydrogel assembled into a flexible sensor can sense various small and large amplitude movements such as nodding, smiling, frowning, etc., and has a wide range of applications in flexible sensors.

Environmentally stable and rapidly polymerized tin-tannin catalytic system hydroxyethyl cellulose hydrogel for wireless wearable sensing.

In recent years, flexible sensors constructed mainly from hydrogels have played an indispensable role in several fields. However, the traditional hydrogel preparation process involves complex and time-consuming steps and the freezing or volatilization of water in the water gel in extreme environments greatly limits the further use of the sensor. Therefore, an ionic conductive hydrogel (SnHTD) was designed, which was composed of tannic acid (TA), metal ions Sn2+, hydroxyethyl cellulose (HEC), and acrylamide (AM) in a deep eutectic solvent (DES) and water binary solvent. It is worth noting that the gel time is shortened to less than 3 min by introducing the Sn-TA redox system. The addition of DES makes the hydrogel have a wide temperature tolerance range (-20 to 60 °C) and the ability to store for a long time (30 days). The introduction of HEC increased the tensile stress of hydrogel from 140.17 kPa to 219.89 kPa. Additionally, the hydrogel also has high conductivity, repeatable adhesion and UV shielding properties. In general, this research opens up a new way for room temperature polymerization of environmentally resistant hydrogel materials and effectively meets the growing demand for wireless wearable sensing.

The prescription design and key properties of nasal gel for CNS drug delivery: A review.

Central nervous system (CNS) diseases are among the major health problems. However, blood-brain barrier (BBB) makes traditional oral and intravenous delivery of CNS drugs inefficient. The unique direct connection between the nose and the brain makes nasal administration a great potential advantage in CNS drugs delivery. However, nasal mucociliary clearance (NMCC) limits the development of drug delivery systems. Appropriate nasal gel viscosity alleviates NMCC to a certain extent, gels based on gellan gum, chitosan, carbomer, cellulose and poloxamer have been widely reported. However, nasal gel formulation design and key properties for alleviating NMCC have not been clearly discussed. This article summarizes gel formulations of different polymers in existing nasal gel systems, and attempts to provide a basis for researchers to conduct in-depth research on the key characteristics of gel matrix against NMCC.

Room Temperature Ca2+-Initiated Free Radical Polymerization for the Preparation of Conductive, Adhesive, Anti-freezing and UV-Blocking Hydrogels for Monitoring Human Movement.

In recent years, conductive hydrogels have received increasing attention as wearable electronics due to the electrochemical properties of conductive polymers combined with the softness of hydrogels. However, conventional hydrogels are complicated to prepare, require high temperature or UV radiation to trigger monomer polymerization, and are frozen at low temperatures, which seriously hinder the application of flexible wearable devices. In this paper, a conductive sensor integrating mechanical properties, adhesion, UV shielding, anti-dehydration, and anti-freeze was prepared based on Ca2+-initiated radical polymerization at room temperature using the synergy of sodium lignosulfonate, acrylamide (AM), and calcium chloride (CaCl2). Metal ions can activate ammonium persulfate to generate free radicals that allow rapid gelation of AM monomers at room temperature without external stimuli. Due to ionic cross-linking and non-covalent interaction, the hydrogels have good tensile properties (1153% elongation and 168 kPa tensile strength), high toughness (758 KJ·m-3), excellent adhesive properties (48.5 kPa), high ionic conductivity (7.2 mS·cm-1), and UV resistance (94.4%). CaCl2 can inhibit ice nucleation, so that the hydrogels have anti-dehydration and frost resistance properties and even at -80 °C can maintain flexibility, high conductivity, and adhesion. Assembled into a flexible sensor, it can sense various large and small movements such as compression, bending, and talking, which is a flexible sensing material with wide application prospects.

Ta-Xi-San Suppresses Atopic Dermatitis Involved in Multitarget Mechanism Using Experimental and Network Pharmacology Analysis.

Atopic dermatitis (AD) is a relapsing and chronic skin inflammation with a common incidence worldwide. Ta-Xi-San (TXS) is a Chinese herbal formula usually used for atopic dermatitis in clinic; however, its active compounds and mechanisms of action are still unclear. Our study was designed to reveal the pharmacological activities, the active compounds, and the pharmacological mechanisms of TXS for atopic dermatitis. Mice were induced by 2,4-dinitrocluorobenzene (DNCB) to build atopic dermatitis model. The pathological evaluation, enzyme-linked immunosorbent assay (ELISA), and hematoxylin and eosin (H&E) assay were performed. The UPLC-Q-Exactive-MSE and network pharmacology analysis were performed to explore active ingredients and therapeutic mechanisms of TXS. TXS treatment decreased levels of immunoglobulin E (IgE), interleukin-4 (IL-4), and tumor necrosis factor-α (TNF-α) in serum induced by DNCB. TXS reduced scratching behavior and alleviated inflammatory pathology of skin and ear. Meanwhile, TXS decreased the spleen index and increased spleen index. The UPLC-Q-Exactive-MSE results showed that 65 compounds of TXS were detected and 337 targets were fished. We collected 1371 AD disease targets, and the compound-target gene network reveled that the top 3 active ingredients were (-)-epigallocatechin gallate, apigenin, and esculetin, and the core target genes were PTGS2, PTGS1, and HSP90AA1. The KEGG pathway and GO analysis showed that TXS remedied atopic dermatitis via PI3K-Akt signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, and Toll-like receptor (TLR) signaling pathway with the regulation of inflammatory response and transcription. Further, we found that the targets of PTGS2 and HSP90AA1 were both elevated in ears and skin of AD model mouse; however, TXS decreased the elevated expressions of PTGS2 and HSP90AA1. Our study revealed that TXS ameliorated AD based on (-)-epigallocatechin gallate, apigenin, and esculetin via targeting PTGS2 and HSP90AA1.

Intelligent hydrogel with both redox and thermo-response based on cellulose nanofiber for controlled drug delivery.

The purpose of this study is to develop a hydrogel with temperature and redox response to control drug delivery. However, the strength of temperature sensitive N-isopropylacrylamide (NIPAM) hydrogel is weak. Therefore, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) oxidized cellulose nanofiber (CNF) is introduced to improve this problem. The compressive strength of hydrogels increased by 360% after CNF addition. Meanwhile, N,N'-bis(acryloyl)cystamine (BACy) is introduced into the hydrogels as a cross-linker, imparting redox responsive properties to the hydrogels. Tumor therapeutic drugs are used as model drugs for in vitro release studies. The drug release rate of hydrogel is regulated by temperature and reducing environment. The maximum cumulative release rate of doxorubicin (DOX) is 39.56%, and the Berberine (BBR) is 99.50% after 60 h. The swelling and transparency of hydrogels showed dramatic changes in the range of 30-40 °C. Cytotoxicity experiments demonstrated that the hydrogel had almost no cytotoxicity.

Proteome profiling reveals the efficacy and targets of sophocarpine against asthma.

Sophocarpine (SPC) as a quinolizidine alkaloid displays powerful effects on inflammatory diseases through regulating multiple targets. Asthma is a complex heterogeneous and inflammatory disease with an increasing incidence worldwide. Here we established a mice asthma model and investigated the effect of SPC. Mice induced by ovalbumin (OVA) exhibits exacerbated Th1/Th2 immune imbalance and allergic lung inflammation. SPC treatment regulated Th1/Th2 cytokines production (IL-4, IL-5 and INF-γ) in BALF, reduced IgE level in serum, inhibited inflammatory cell infiltration, and improved the lung tissue pathology. Proteomic results showed that 5064 proteins in lung tissue were detected and among them 223 preliminary therapeutic targets of SPC were selected. Subsequently, excluding non-human genes, 109 targets with established crystal structures were harvested. Meanwhile, the molecular docking results showed that the binding energy of 87 targets with SPC was varied from -9.72 kcal/mol to 227.16 kcal/mol. Further, SPC suppressed arrb2, anxa1, myd88 and sphk1 expression and activated p-stat1. All of the five targets based on the screened results of proteomics and molecular docking are critical in allergic asthma. Thus, our data revealed that SPC alleviated bronchial asthma via targeting multi-targets.

Preparation and properties of a highly elastic galactomannan- poly(acrylamide- N, N-bis (acryloyl) cysteamine) hydrogel with reductive stimuli-responsive degradable properties.

An oxidation-reduction responsive degradable highly elastic galactomannan hydrogel was synthesized from galactomannan (GA), N,N-bis (acryloyl) cysteamine (BAC) and acrylamide by grafting polymerization in aqueous solution. The microstructure, degradability and mechanical properties of the hydrogels were emphatically investigated using Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), ultraviolet spectroscopy and differential scanning calorimetry (DSC). The mechanical properties of hydrogels can be improved by adjusting the content of GA. Continuous cyclic compression tests showed that the hydrogel did not rupture under 60 %,70 %,80 % strain and quickly recovered to its original shape. The degradation rate and drug release rate of hydrogel can be adjusted by the concentration of the reductant and the reduction time. These hydrogels broaden the scope of application of GA and can be tuned with a broad range of mechanical, degradation and release properties and therefore hold potential applications in drug carriers, tissue engineering scaffolds, extracellular matrix and other fields.

Preparation and Drug Release Properties of a Thermo Sensitive GA Hydrogel.

A high-strength galactomannan (GA)-based hydrogel with thermal response and pH response is introduced in this paper. GA, N-isopropylacrylamide (NIPAM), N-[3-dimethylamino)propyl]methylacrylamide (DMAPMA), and montmorillonite were used to form hydrogels through a simple mixed static system. Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM) were used to characterize the structure and properties of the hydrogels. The compressive strength of the the hydrogel increased from 23.9 to 105.61 kPa with the increase of GA dosage from 0 to 1.5 wt%. When the NIPAM content in the monomer increased from 75% to 95%, the lower critical solution temperature (LCST) of the hydrogel changed from 36.5 to 45.8 °C. When the monomer content was higher than 10wt%, the swelling kinetics of the sample changed from the second-order equation to the first-order equation. With the increase of the proportion of NIPAM monomer, the release rate of bovine serum album in the early stage was faster, and the cumulative release rate was close to 100%.The release rate of bovine serum albumin at 37 °C was higher than that at 25 °C. The release rate of the hydrogel containing bovine serum albumin was the fastest under the condition of pH 7.4, followed by those at pH 6.6 and pH 5.0. The results showed that this thermal-responsive hydrogel has potential applications as a drug carrier for colon delivery.

The Trigeminal Pathway Dominates the Nose-to-Brain Transportation of Intact Polymeric Nanoparticles: Evidence from Aggregation-Caused Quenching Probes.

Nasal drug delivery is a fascinating approach to bypass the blood-brain barrier, which instead directly transports drug molecules to the brain from the nasal cavity along the olfactory and trigeminal nerves. However, the feasibility of nose-to-brain transportation of intact nanoparticles and the possible corresponding pathways remain poorly understood. The purpose of the present study is to explore the intranasal fate of curcumin (Cur)-loaded polycaprolactone nanoparticles (PCL NPs) via fluorescent bioimaging strategies. The behavior of intact nanoparticles was tracked by aggregation-caused quenching (ACQ) probes, which provide on-to-off fluorescent switching from loaded to released states. Evidence for the translocation of intact nanoparticles and Cur was collected either via live imaging or ex vivo histological examination in rats after nasal administration. Intact PCL NPs, irrespective of whether or not they are PEGylated, cannot enter into the olfactory bulb from the nasal cavity, whereas free Cur molecules that are released from the nanoparticles can diffuse into the olfactory bulb. Both PCL NPs and PEGylated PCL NPs carrying Cur can permeate into the mucosa and the trigeminal nerves. Although PEGylation improves the nasal retention of NPs and mucus-penetration, it reduces permeation of NPs into the trigeminal nerves. Transportation of NPs along the trigeminal nerves is slow. Neither the carriers nor the Cur signals are found in the brain at 1 h post-administration. However, starting at 2 h post-administration, both intact nanoparticles and Cur are transported into the brainstem, as exemplified by the presence of Cur-loaded PEGylated PCL NPs. Nanoparticles reaching the brainstem can further distribute to other parts of the brain such as the middle brain. We conclude that the trigeminal nerve pathway, instead of the olfactory nerve route, dominates the nose-to-brain delivery of intact polymeric nanoparticles.

Advances in Pharmaceutical Strategies Enhancing the Efficiencies of Oral Colon-Targeted Delivery Systems in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a common disease characterized by chronic inflammation in gastrointestinal tracts, which is primarily treated by administering anti-inflammatory and immunosuppressive drugs that inhibit the burden of intestinal inflammation and improve disease-related symptoms. However, the established therapeutic strategy has limited therapeutic efficacy and adverse drug reactions. Therefore, new disease-targeting drug-delivery strategies to develop more effective treatments are urgent. This review provides an overview of the drug-targeting strategies that can be used to treat IBD, and our recent attempts on the colon-specific delivery system (Pae-SME-CSC) with a paeonol-loaded self-microemulsion (Pae-SMEDDS) are introduced.

Beneficial anti-inflammatory effect of paeonol self-microemulsion-loaded colon-specific capsules on experimental ulcerative colitis rats.

Paeonol, as the main phenolic compound isolated from the Chinese herbs, has been confirmed to present anti-inflammatory effects on ulcerative colitis (UC) in our previous study. However, its poor solubility has hindered its development of being a favourable pharmaceutical product in treating colon diseases. In this study, we prepared the colon-specific delivery system (Pae-SME-CSC) with paeonol-loaded self-microemulsion (Pae-SMEDDS), and evaluated its in vitro and in vivo properties, especially the anti-inflammatory effects on UC rats. The anti-inflammatory effects were evaluated by the disease activity index, colon weight/length ratio, and macroscopic damage and microscopic damage scores. IL-17, IL-6, and TGF-ß1 levels were also determined by enzyme-linked immunosorbent assay. The results showed that Pae-SME-CSC had good colon-targeting property in vivo and in vitro, with favourable stability. Efficacy evaluation showed that the dose of the paeonol group (100 mg/kg) exhibited no significant effect on UC (p > .05, compared with the model group), while the Pae-SME-CSC group (100 mg/kg) showed better anti-UC effects (p < .01 or p < .05), and its anti-inflammatory effect was close to that of the paeonol group (200 mg/kg) (p > .05). These results indicated that the developed Pae-SME-CSC was suitable for colon-specific drug delivery.

Study on the physicochemical properties and anti-inflammatory effects of paeonol in rats with TNBS-induced ulcerative colitis.

Paeonol, an active component from Paeonia suffruticosa Andr., has a variety of biological activities, such as vascular endothelial cell protection, anti-oxidation, and anti-inflammation. The aim of this study was to investigate the basic physicochemical properties of paeonol, including solubility, oil-water partition coefficient, and permeability. Then evaluated the anti-inflammatory effects of paeonol were evaluated on 2,4,6-trinitrobenzenesulfonic acid-induced ulcerative colitis in rats. The rats were divided randomly into 6 groups, namely, normal, model, paeonol-treated (100, 200, and 400mg/kg), and positive. Each group had 10 rats. Inhibition effects were evaluated by the disease activity index (DAI), colon weight/length ratio, as well as macroscopical and histological evaluations. Serum interleukin (IL)-17, IL-6 and transforming growth factor beta 1 (TGF-ß1) levels were determined by enzyme-linked immunosorbent assay. The solubility and oil-water partition coefficient of paeonol in different phosphate buffer solutions were 284.06-598.23 and 461.97-981.17µg/mL, respectively. The effective passive permeability value Pe was 23.49×10-6cm/s. In terms of anti-inflammatory results, compared with the model group, treatment with 200 and 400mg/kg doses of paeonol had significantly decreased DAI, colon weight/length ratio, and macroscopic and histopathological scores. Furthermore, the serum levels of IL-17 and IL-6 were significantly reduced, whereas the TGF-ß1 level was increased in the two paeonol-treated groups (medium- and high-dose group). Therefore, paeonol had poor water solubility, but oral absorption was good. In addition, paeonol had therapeutic effects on ulcerative colitis, and the therapeutic efficacy was dose dependent. The results presented in this study provide evidence for the development of a novel therapeutic agent in the treatment of UC. However, whether this agent could have therapeutic benefit or adverse effects in human IBD remains to be fully explored.

Fast Simultaneous Determination of 13 Nucleosides and Nucleobases in Cordyceps sinensis by UHPLC-ESI-MS/MS.

A reliable ultra-high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UHPLC-ESI-MS/MS) method for the fast simultaneous determination of 13 nucleosides and nucleobases in Cordyceps sinensis (C. sinensis) with 2-chloroadenosine as internal standard was developed and validated. Samples were ultrasonically extracted in an ice bath thrice, and the optimum analyte separation was performed on an ACQUITY UPLC(TM) HSS C18 column (100 mm × 2.1 mm, 1.8 µm) with gradient elution. All targeted analytes were separated in 5.5 min. Furthermore, all calibration curves showed good linear regression (r > 0.9970) within the test ranges, and the limits of quantitation and detection of the 13 analytes were less than 150 and 75 ng/mL, respectively. The relative standard deviations (RSDs) of intra- and inter-day precisions were <6.23%. Recoveries of the quantified analytes ranged within 85.3%-117.3%, with RSD < 6.18%. The developed UHPLC-ESI-MS/MS method was successfully applied to determine nucleosides and nucleobases in 11 batches of C. sinensis samples from different regions in China. The range for the total content in the analyzed samples was 1329-2057 µg/g.